Amino acid chelates for delivery of minerals to biological tissues are described in U.S. Pat. No. 4,863,898 and U.S. Pat. No. 4,599,152 (Albion). Amino acid chelates in this context refers to the product resulting from the reaction of a polypeptide, dipeptide or naturally occurring alpha amino acid with a metal ion having a valence of two or more to form a ring structure in which the positive electrical charges of the metal ion are neutralized by the electrons available through the carboxylate or free amino groups of the alpha amino acid. As described by U.S. Pat. No. 4,863,898, chelate formation through neutralization of the positive charges of the divalent metal ions can be through the formation of ionic, covalent or coordinate covalent bonding. U.S. Pat. No. 4,863,898 states that it provides an advantage over the prior art metal chelates, which are effective to increase metal content in biological tissues generally, by providing metal chelates targeted to specific tissues. Manganese, calcium, iron, magnesium, copper, and zinc amino acid chelates are among those described.
Polyunsaturated fatty acids of the omega-3 series (“omega-3 fatty acids”) have shown a wide spectrum of biological activities suggesting their possible usefulness in treating a range of diseases and disorders including metabolic disorders, cardiovascular complications, inflammatory diseases, central nervous system disorders, and ophthalmic complications. There are three major types of omega-3 fatty acids involved in the human physiology: α-linolenic acid (ALA; found in plant oils), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) (both commonly found in marine oils). Marine algae and phytoplankton are also sources of omega-3 fatty acids. Common sources of plant oils containing the omega-3 ALA fatty acid include walnut, edible seeds, clary sage seed oil, algal oil, flaxseed oil, Sacha Inchi oil, Echium oil, and hemp oil, while sources of animal omega-3 EPA and DHA fatty acids include fish oils, egg oil, squid oils, and krill oil. Often these primary omega-3 fatty acids are present with numerous minor omega-3 fatty acids as mixtures. But the poor aqueous solubility of omega-3 fatty acids limits their utility as therapeutic agents and as nutraceutical additives to food and drink due to a phenomenon referred to as solubility-limited absorption which limits the plasma levels that can be achieved following oral administration. In fact, the omega-3 fatty acids are essentially insoluble in water and both the free acid and sodium salt forms create soap-like emulsions when mixed with water. Thus, although omega-3 fatty acids are absorbed following oral administration, the relatively low plasma levels achieved cannot be increased simply by increasing the dose administered.
In addition to their poor aqueous solubility, omega-3 fatty acids suffer from susceptibility to lipid oxidation. This oxidation leads to formation of undesirable fishy and rancid off-flavors that render compositions comprising them less palatable.
WO 2014011895 describes fatty acid salts of eicosapentaenoic acid (EPA) with lysine or docosahexaenoic acid (DHA) or EPA with metformin, piperazine, and meglumine.
US 2011237813 (Jost Chemical Co.) describes mineral co-salts of polyunsaturated fatty acids and a non-fatty acid co-anion formed as a precipitate.
WO 2004082402 (Novartis AG) describes a combination, such as a combined preparation or pharmaceutical or nutritional composition, respectively, which comprises at least one cis-polyunsaturated fatty acid, at least one amino acid, and optionally at least one diabetes medicine for simultaneous, separate or sequential use in the prevention, delay of progression or treatment of diseases, especially metabolic disorders and in particular type 2 diabetes.
There is a need to develop new compositions able to deliver omega-3 fatty acids at much higher plasma levels than is possible using the currently available free fatty acid, sodium salt, or ester forms, in order to fulfill the therapeutic and nutritional promise of these compounds and translate the many promising in vitro and cellular pharmacology observations into clinical and general health benefits. The present invention addresses these needs.